To elucidate the role of apoptotic cell death in human corpus luteum (CL) regression, human CL during the menstrual cycle and early pregnancy were isolated and processed for biochemical (radio-labeling) analysis of DNA integrity. Total DNA extracted from human CL of the early luteal phase contained predominantly high mol wt DNA, whereas CL of the midluteal phase exhibited the appearance of DNA cleavage into low mol wt ladders characteristic of apoptosis. Although apoptotic DNA cleavage of human CL significantly increased from the midluteal phase to the late luteal phase (P < 0.05), CL of early pregnancy did not exhibit apoptotic DNA fragmentation by biochemical analysis. In situ analysis of DNA fragmentation revealed that both large and small luteal cells exhibited DNA cleavage in human CL of the midluteal and late luteal phases and in regressive CL. The present findings suggest that 1) human luteal regression may be mediated by apoptosis; and 2) CL of early pregnancy may be rescued from luteolysis through inhibiting the occurrence of apoptotic luteal cell death.

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To investigate apoptotic changes, we studied the cleavage of DNA in the uterine endometrium obtained from regularly cycling women by a quantitative end labeling of DNA gel fractionation and in situ analysis. The ladder pattern characteristic of the apoptotic cleavage of DNA into fragments of low mol wt was identified at three different phases of the cycle, namely the early proliferative, late secretory, and menstrual phases. However, DNA of high mol wt was predominant in the endometrium during the late proliferative, early secretory, and midsecretory phases. Our analysis in situ revealed that cells undergoing apoptosis were scattered in the functional layer of the early proliferative endometrium. However, apoptotic cells were no longer detectable during the late proliferative phase, and none was observed until the midsecretory phase. At the beginning of the late secretory phase, apoptosis reappeared in the stromal cells and spread gradually to almost all components of the functional layer. By contrast, cells in the basal layer showed no evidence of apoptosis throughout the menstrual cycle. The present study demonstrates that apoptosis occurs in specific populations of cells during three phases of the human endometrial cycle. Our results indicate, moreover, that apoptosis might have an important role in the regulation of the menstrual cycle in women.

To investigate apoptotic changes, we studied the cleavage of DNA in the uterine endometrium obtained from regularly cycling women by a quantitative end labeling of DNA gel fractionation and in situ analysis. The ladder pattern characteristic of the apoptotic cleavage of DNA into fragments of low mol wt was identified at three different phases of the cycle, namely the early proliferative, late secretory, and menstrual phases. However, DNA of high mol wt was predominant in the endometrium during the late proliferative, early secretory, and midsecretory phases. Our analysis in situ revealed that cells undergoing apoptosis were scattered in the functional layer of the early proliferative endometrium. However, apoptotic cells were no longer detectable during the late proliferative phase, and none was observed until the midsecretory phase. At the beginning of the late secretory phase, apoptosis reappeared in the stromal cells and spread gradually to almost all components of the functional layer. By contrast, cells in the basal layer showed no evidence of apoptosis throughout the menstrual cycle. The present study demonstrates that apoptosis occurs in specific populations of cells during three phases of the human endometrial cycle. Our results indicate, moreover, that apoptosis might have an important role in the regulation of the menstrual cycle in women.

To review clinical outcomes and therapeutic varieties, we were invited to submit data from the patients who were treated for uterine sarcomas in Japan from 1990 to 2003. Uterine sarcomas were defined as leiomyosarcoma (LMS), endometrial stromal sarcoma (ESS), and carcinosarcoma (CS). Of a total of 97 patients, 36 (37.1%) were diagnosed with LMS of the uterine corpus, 15 (15.5%) with ESS, 46 (47.4%) with CS. Median age at diagnosis was 59 (21-85) years. Clinical stages based on FIGO were 41 (42.3%) with stage I disease, 6 (6.2%) with staged II, 34 (35.1%) with stage III, and 16 (16.5%) with stage IV. The median follow-up period for all patients was 13 (1-108) months and median disease-free period was 9 (0-96) months. The 1-year survival rate and disease-free survival (DFS) rate were calculated in patients with all sarcomas (overall survival [OAS], 61.3%; DFS, 46.6%). Statistical analysis showed that younger age (less than 50 years), early stage (stages I and II), and surgical procedure (extended hysterectomy [EH] and radical hysterectomy [RH]) were associated with significantly better OAS. Histologic types did not affect the survival period. In conclusion, aggressive surgery including EH or RH at the time of initial operation offers the possibility of prolonged survival.